Sorting Nexin 27 (SNX27) is a hippocampal-enriched endosome-associated cargo adaptor that shapes endocytic events underlying neuronal function and excitability, being relevant for cognitive and reward-associated processes. There is an association of SNX27 with glutamatergic and dopaminergic signaling, as SNX27 modulation alters hippocampal glutamatergic transmission and dopaminergic neurons GABABR-activated GIRK signaling. Notwithstanding, the impact of SNX27 modulation on neuronal circuitry function or behavior remains elusive. In this work we deleted SNX27 in different neuronal types in order to understand the relevance of this protein for the circuit and for different behavioral dimensions. We performed SNX27 hippocampal specific depletion, using a cre virus bilateral injection in the dorsal and ventral hippocampus in SNX27flox/flox mice. For dopaminergic SNX27 neuronal silencing, we crossed SNX27flox/flox with DAT-Cre+/- mice. Remarkably, silencing SNX27 in these two neuronal subtypes prompted similar behavioral outcomes. Cognitive impairments, particularly affecting spatial and recognition memory, were observed in all models. Moreover, both models exhibited heightened cocaine-induced locomotor sensitization. These findings highlight the importance of SNX27 in the integrity of different neuronal circuits, emphasizing that additional studies are needed to understand the role of this protein in the brain.